The phase II SAVANNAH study

The 2025 edition of the European Lung Cancer Conference (ELCC) featured the primary results of the phase II SAVANNAH study, evaluating the combination of osimertinib and savolitinib in EGFR-mutant and MET-dysregulated advanced non-small cell lung cancer (NSCLC) who progressed on first line osimertinib. In this video, Prof Dr Myung-Ju Ahn, Medical oncologist at the Sungkyunkwan University School of Medicine in Seoul, talks us through the key take-aways from this presentation.

Savolitinib is an oral, highly selective tyrosine kinase inhibitor targeting MET. When combined with osimertinib, this agent may overcome acquired MET-driven resistance in EGFR-mutant advanced NSCLC patients progressing on osimertinib. In the phase II SAVANNAH study, EGFR-mutant advanced NSCLC patients with MET overexpression and/or amplification who progressed on osimertinib were treated with savolitinib (300 mg BID) in combination with osimertinib (80 mg QD). Initially, the study used a threshold for MET overexpression of IHC 3+ in more than 50% of tumor cells, or a FISH score of 5+ (i.e., 5 MET copies). In an update of the protocol, this definition was changed to IHC3+ in more than 90% of tumor cells or FISH10+.

The safety analysis set for the presented analysis included 101 patients who received savolitinib 300 mg BID in combination with osimertinib. The efficacy analysis focussed on 80 of these patients with an IHC3+/≥90% and/or FISH10+ status. The median age of patients in the efficacy analysis was 66 years, 53% were never smokers and 39% had brain metastases at baseline. The objective response rate (ORR) by blinded independent review was reported at 55%, with a medain response duration of 9.9 months. The median progression-free survival (PFS) reached 7.7 months, which is better than what can be achieved in this setting with platinum-based chemotherapy.

With respect to safety, the savolitinib-osimertinib combination was associated with a grade ≥3 treatment-related adverse event rate of 32%. Adverse events led to savolitinib treatment discontinuation in 16% of the patients. The most common adverse events (all-cause) were peripheral oedema (56%, 11% grade ≥3), nausea (45%, 2% grade ≥3) and diarrhea (33%, 3% grade ≥3). 

Based on these results, Prof Ahn concludes that, if confirmed in a randomized phase III trial, savolitinib plus osimertinib may offer a new chemotherapy-free treatment option for patients with EGFR-mutant and MET-dysregulated advanced NSCLC progressing on first line osimertinib.